Chlamydia trachomatis e Inmunidad

Transient detection of Chlamydial-specific Th1 memory cells in the peripheral circulation of women with history of Chlamydia trachomatis genital tract infection.

Vicetti Miguel RD¹, Reighard SD, Chavez JM, Rabe LK, Maryak SA, Wiesenfeld HC, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.

 

Abstract

PROBLEM:

Development of safe and effective Chlamydia trachomatis vaccines requires better understanding of the host immune responses elicited by natural infection.

METHOD OF STUDY:

Peripheral blood mononuclear cells isolated from women with or without history of genital tract chlamydial infection were stimulated with inactivated C. trachomatis elementary bodies (EB) in ELISPOT assays that enumerated frequencies of cells producing interferon (IFN)-γ or interleukin (IL)-17.

RESULTS:

IFN-γ-positive cells were highest among women sampled 30-60 days after diagnosis of C. trachomatis infection and treatment initiation, while the numbers of IFN-γ-positive cells were equally low among uninfected women and women sampled <30 or >60 days after diagnosis of infection. Conversely, IL-17-positive cell numbers were uniformly low among all participants.

CONCLUSION:

Dramatically reduced numbers of Chlamydia-specific Th1 memory cells in the peripheral circulation of study participants sampled more than 2 months after diagnosis, and initiation of treatment provides new insight into the results from C. trachomatis vaccine trials, in which immunization with EB provided only short-lived protection. Our results also suggest that an effective vaccine against this weakly antigenic intracellular pathogen will need to generate immunological memory more durable than that elicited by natural infection.

© 2012 John Wiley & Sons A/S.

Am J Reprod Immunol. 2012 Dec;68(6):499-506. doi: 10.1111/aji.12008. Epub 2012 Aug 31.

http://onlinelibrary.wiley.com/doi/10.1111/aji.12008/abstract;jsessionid=B95D7E5E29926F60FB0D65C3E2DB60D8.f02t01

Md. Rodolfo Vicetti. Ex-miembro del GII. 

Chlamydia trachomatis e Inmunidad

Hypothesis: Chlamydia trachomatis infection of the female genital tract is controlled by Type 2 immunity.

Vicetti Miguel RD¹, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

 

Abstract

Chlamydia trachomatis is an obligate intracellular bacterium sexually transmitted to more than 90 million individuals each year. As this level of infectivity implies, C. trachomatis is a successful human parasite; a success facilitated by its ability to cause asymptomatic infection. Host defense against C. trachomatis in the female genital tract is not well defined, but current dogma suggests infection is controlled largely by T(H)1 immunity. Conversely, it is well established that T(H)2 immunity controls allergens, helminths, and other extracellular pathogens that cause repetitive or persistent T cell stimulation but do not induce the exuberant inflammation that drives T(H)1 and T(H)17 immunity. As C. trachomatis persists in female genital tract epithelial cells but does not elicit over tissue inflammation, we now posit that defense is maintained by Type 2 immune responses that control bacterial growth but minimize immunopathological damage to vital reproductive tract anatomy. Evaluation of this hypothesis may uncover novel mechanisms by which Type 2 immunity can control growth of C. trachomatis and other intracellular pathogens, while confirmation that T(H)2 immunity was selected by evolution to control C. trachomatis infection in the female genital tract will transform current research, now focused on developing vaccines that elicit strong, and therefore potentially tissue destructive, Chlamydia-specific T(H)1 immunity.

Copyright © 2012 Elsevier Ltd. All rights reserved.

Med Hypotheses. 2012 Dec;79(6):713-6. doi: 10.1016/j.mehy.2012.07.032. Epub 2012 Sep 15.

http://www.sciencedirect.com/science/article/pii/S0306987712003568

Md. Rodolfo Vicetti. Ex-miembro del GII.

Chlamydia trachomatis e Inmunidad

Brefeldin A, but not monensin, enables flow cytometric detection of interleukin-4 within peripheral T cells responding to ex vivo stimulation with Chlamydia trachomatis.

Vicetti Miguel RD¹, Maryak SA, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA. rdv4@pitt.edu

 

Abstract

Intracellular cytokine staining (ICS) assay optimization should include selection of suitable cytokine secretion inhibitors. Here, peripheral blood mononuclear cells (PBMC) from women with proven history of C. trachomatis genital tract infection were used to compare the ability of brefeldin A (BFA) and monensin (MN) to concurrently trap interferon-γ (IFN-γ), tumor necrosis factor (TNF), interleukin (IL)-4, and IL-17 within T cells responding to ex vivo stimulation with chlamydial antigen. While flow cytometric analyses showed similar intracellular levels of TNF, IFN-γ, and IL-17 among T cells treated with BFA or both BFA and MN, markedly more IL-4 was found inside T cells treated with BFA compared to those that received MN or BFA and MN. The latter findings oppose current ICS recommendations informing that ICS results are unaffected by concomitant use of BFA and MN, and also suggests that MN may be an unsuitable cytokine secretion inhibitor for ICS assays designed to measure intracellular IL-4 accumulation.

Copyright © 2012 Elsevier B.V. All rights reserved.

J Immunol Methods. 2012 Oct 31;384(1-2):191-5. doi: 10.1016/j.jim.2012.07.018. Epub 2012 Jul 29.

http://www.sciencedirect.com/science/article/pii/S0022175912002293

Md. Rodolfo Vicetti. Ex-miembro del GII.

Célula Dendríticas y Medroxyprogesterona

Dendritic cell activation and memory cell development are impaired among mice administered medroxyprogesterone acetate prior to mucosal herpes simplex virus type 1 infection.

Vicetti Miguel RD¹, Hendricks RL, Aguirre AJ, Melan MA, Harvey SA, Terry-Allison T, St Leger AJ, Thomson AW, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.

 

Abstract

Epidemiological studies indicate that the exogenous sex steroid medroxyprogesterone acetate (MPA) can impair cell-mediated immunity, but mechanisms responsible for this observation are not well defined. In this study, MPA administered to mice 1 wk prior to HSV type 1 (HSV-1) infection of their corneal mucosa impaired initial expansion of viral-specific effector and memory precursor T cells and reduced the number of viral-specific memory T cells found in latently infected mice. MPA treatment also dampened expression of the costimulatory molecules CD40, CD70, and CD80 by dendritic cells (DC) in lymph nodes draining acute infection, whereas coculture of such DC with T cells from uninfected mice dramatically impaired ex vivo T cell proliferation compared with the use of DC from mice that did not receive MPA prior to HSV-1 infection. In addition, T cell expansion was comparable to that seen in untreated controls if MPA-treated mice were administered recombinant soluble CD154 (CD40L) concomitant with their mucosal infection. In contrast, the immunomodulatory effects of MPA were infection site dependent, because MPA-treated mice exhibited normal expansion of virus-specific T cells when infection was systemic rather than mucosal. Taken together, our results reveal that the administration of MPA prior to viral infection of mucosal tissue impairs DC activation, virus-specific T cell expansion, and development of virus-specific immunological memory.

J Immunol. 2012 Oct 1;189(7):3449-61. Epub 2012 Aug 31.

http://www.jimmunol.org/content/189/7/3449.long


Md. Rodolfo Vicetti. Ex-miembro del GII.

Dermatología e Inmunología

Mastocitos y basófilos y sus nuevas funciones en inmunología

 Julio E Valdivia-Silva 

1Chemokines Biology Research Laboratory, Instituto de Investigaciones Biomédicas, UNAM, México D.F., México.

ABSTRACT 

Mast cells and basophils have demonstrated to have both beneficial and detrimental functions for the immune system. Additionally to their classic role in pro-inflammatory responses to allergens, they are also involved directly in immunity against different pathogens. Because there are few animals models developed to investigate these cells in vivo, their functions during health and disease remain poorly understood. This review gives a short glance in the development and functional status of mast cells and basophils focusing on immunology concepts necessary to get a major understanding of the mechanisms of disease in different pathological states. 

DERMATOL PERU 2012; VOL 23

http://sisbib.unmsm.edu.pe/bvrevistas/dermatologia/v23_n2/pdf/a04v23n2.pdf

Md PhD Julio Valdivia Silva. Fundador del GII

 

 

HSV-2 y Vaginosis Bacterial

Recalcitrance of bacterial vaginosis among herpes-simplex-virus-type-2-seropositive women.

Stoner KA¹, Reighard SD, Vicetti Miguel RD, Landsittel D, Cosentino LA, Kant JA, Cherpes TL.

¹Departments of Obstetrics and Gynecology and Reproductive Sciences Pediatrics Medicine Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

 

Abstract

AIM:

The multifactorial etiology of bacterial vaginosis (BV) impedes development of effective treatment and prevention strategies. Herein, we evaluated the effects of herpes simplex virus type 2 (HSV-2), a suspected BV risk factor, on vaginal flora composition.

MATERIALS AND METHODS:

  Correlations between HSV-2 infection and BV were prospectively explored among 12 HSV-2-seropositive women with asymptomatic BV who were asked to collect daily vaginal swab specimens for Gram stain analysis of vaginal flora and determination of HSV-2 shedding frequencies during the 1month before and after metronidazole therapy.

RESULTS:

Unlike prior longitudinal studies that reported rapid fluctuations in vaginal flora composition and frequent episodes of spontaneously resolving BV, we found that 99.4% (310/312) of vaginal smears collected before initiation of metronidazole were consistent with a diagnosis of BV. Effectiveness of metronidazole therapy was also much lower than previously reported in studies not restricting enrollment to HSV-2-seropositive women; we observed a BV recurrence rate of 89% in the first month after completion of therapy while the median time to this recurrence occurred only 14days after treatment.

CONCLUSIONS:

Our study demonstrates BV recalcitrance among HSV-2-infected women and provides additional evidence for a linkage between this chronic viral infection and abnormal vaginal flora. Additional work will be needed to define mechanisms responsible for this correlation and to determine if vaginal flora health of HSV-2-infected women is improved by medications that suppress HSV-2 shedding.

© 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

J Obstet Gynaecol Res. 2012 Jan;38(1):77-83. doi: 10.1111/j.1447-0756.2011.01697.x. Epub 2011 Dec 5.

http://onlinelibrary.wiley.com/doi/10.1111/j.1447-0756.2011.01697.x/abstract;jsessionid=54A78C4B43F9813B882574F362F23AC8.f04t03

Md. Rodolfo Vicetti. Ex-miembro del GII.